The immune system is critical to the survival of vertebrates in an environment full of pathogenic microorganisms. Individuals lacking an immune response through inborn genetic defects, exposure to chemotherapeutic agents or through infection by such viruses as human immunodeficiency virus (HIV), succumb to infections that an individual with a healthy immune system would readily survive. However, the immune system is not always beneficial to the organism. Its dysregulation leads to a variety of pathogenic conditions, including autoimmunity and tumors. The immune system also serves as a barrier for the transplantation of foreign grafts, such as those comprising cells, tissues or organs taken from another individual, a process that can treat a variety of pathogenic disorders, including autoimmunity, replace failed organs in end terminal diseases and treat a variety of hematopoietic disorders via bone marrow transplantation. These applications require either the suppression of the immune system or to “educate” the immune system not to react to self-antigens in the case of autoimmunity and foreign antigens in the case of transplantation.
At the present time, most of the treatment regimens in the fields of autoimmunity and transplantation primarily relay on the suppression of the immune system via the chronic use of variety of immunosuppressive pharmacological agents. Although these drugs are effective in reducing the severity of autoimmune and rejection episodes, they are nonspecific and fail to create a state of permanent antigen-specific tolerance. Their continuous use is therefore required to keep the pathogenic reactions under control. Continuous exposure of the individual to these immunosuppressive agents is, however, associated with a significantly increased risk of opportunistic infections and malignancies. Additionally, these nonspecific immunosuppressive agents can induce serious and undesirable pharmacological side effects in the host. It would, therefore, be very desirable to be able to “teach” the immune system to tolerate selected antigens of interest for the treatment of autoimmunity and induction of transplantation tolerance. The need remains to develop more selective and long-lasting methods to regulate the immune response.